OBJECTIVES: To assess the public health impact of the quadrivalent (6,11,16,18) HPV vaccination program for São Paulo, Brazil. METHODS: A published mathematical model of the transmission dynamics of HPV infection and disease was adapted for São Paulo, Brazil.  The model captured direct protective effects of vaccination and indirect effects (herd immunity).  Model inputs were used from Brazil or the Latin/America region when available; otherwise, the default values in the original model were used. Maintaining current cervical cancer screening practices in Brazil, we evaluated two strategies: routine vaccination of females by age 12 (S1), and S1 combined with a temporary (5 years) female catch-up program for age 12–24 years (S2).  The vaccine coverage rates were 85% for the routine and 95% by age 26 years for the catch-up vaccination programs.  RESULTS: Comparing S1 to no vaccination, we estimated the cumulative percent (absolute cases) reduction in HPV 6/11/16/18-related incident genital warts-female, genital warts-male, cervical intraepithelial neoplasia (CIN) grade 1,  CIN 2/3, cervical cancer cases, and cervical cancer deaths would be 78% (2,488,240), 67% (2,166,770), 68% (360,235), 65% (1,154,566), 47% (135,810), and 44% (39,147), respectively, over 100 years.  Compared to S1, S2 provided additional cumulative percent (absolute cases) reduction of 9% (273,866), 11% (357,728), 7% (39,455), 7% (131,861), 7% (19,620), and 7% (6,009) in HPV 6/11/16/18-related incident genital warts-female, genital warts-male, CIN 1, CIN 2/3, cervical cancer cases, cervical cancer deaths. CONCLUSIONS: A prophylactic quadrivalent HPV vaccination program for females in Sao Paulo, Brazil can substantially reduce the incidence of cervical cancer, CIN, and genital warts.  Female catch up vaccination may provide greater reductions in HPV-related diseases.